Open Access Research article

mtDNA haplogroup J Modulates telomere length and Nitric Oxide production

Mercedes Fernández-Moreno1, María Tamayo2, Angel Soto-Hermida1, Alejandro Mosquera2, Natividad Oreiro1, Carlos Fernández-López1, José Luis Fernández2, Ignacio Rego-Pérez1* and Francisco J Blanco134*

Author Affiliations

1 INIBIC-Complejo Hospitalario Universitario A Coruña (CHUAC). Rheumatology Division, As Xubias 84, 15006-A Coruña, Spain

2 INIBIC-Complejo Hospitalario Universitario A Coruña (CHUAC). Genetics Unit, As Xubias 84, 15006-A Coruña, Spain

3 Proteo-Red/ISCIII. Madrid. Spain

4 CIBER-BBN-ISCIII. Madrid. Spain

For all author emails, please log on.

BMC Musculoskeletal Disorders 2011, 12:283  doi:10.1186/1471-2474-12-283

Published: 15 December 2011

Abstract

Background

Oxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Therefore, the goal of this work is to describe the difference in telomere length of peripheral blood leukocytes (PBLs) and Nitric Oxide (NO) production between mitochondrial DNA (mtDNA) haplogroup J and non-J carriers, as indirect approaches of oxidative stress.

Methods

The telomere length of PBL was analyzed in DNA samples from 166 healthy controls (114 J and 52 non-J) and 79 OA patients (41 J and 38 non-J) by means of a validated qPCR method. The NO production was assessed in 7 carriers of the haplogroup J and 27 non-J carriers, by means of the colorimetric reaction of the Griess reagent in supernatants of cultured chondrocytes. Inducible nitric oxide synthase (iNOS) mRNA from these samples was analyzed by qPCR. Appropiated statistical analyses were performed

Results

Carriers of the haplogroup J showed a significantly longer telomere length of PBLs than non-J carriers, regardless of age, gender and diagnosis (p = 0.025). Cultured chondrocytes carrying the mtDNA haplogroup J also showed a lower NO production than non-J carriers (p = 0.043). No significant correlations between age and telomore length of PBLs were detected neither for carriers of the haplogroup J nor for non-J carriers. A strong positive correlation between NO production and iNOS expression was also observed (correlation coefficient = 0.791, p < 0.001).

Conclusion

The protective effect of the mtDNA haplogroup J in the OA disease arise from a lower oxidative stress in carriers of this haplogroup, since this haplogroup is related to lower NO production and hence longer telomere length of PBLs too.

Keywords:
mitochondria; osteoarthritis; cartilage; arthritis; nitric oxide; telomere